See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/264428168
Short Report: Contact with ruminants is associated with esophageal squamous cell carcinoma risk Article in International Journal of Cancer · August 2014 DOI: 10.1002/ijc.29109
CITATION
READS
1
94
12 authors, including: Ramin Shakeri
Shahin Merat
Tehran University of Medical Sciences
Tehran University of Medical Sciences
58 PUBLICATIONS 879 CITATIONS
121 PUBLICATIONS 2,240 CITATIONS
SEE PROFILE
SEE PROFILE
Farin Kamangar
Reza Malekzadeh
Morgan State University
Tehran University of Medical Sciences
182 PUBLICATIONS 7,523 CITATIONS
702 PUBLICATIONS 18,139 CITATIONS
SEE PROFILE
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
Pancreatobiliary disorders View project
Chronic disease (Non communicable disease) prevention at population liver View project All content following this page was uploaded by Reza Malekzadeh on 05 October 2014. The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately.
Short Report: Contact with ruminants is associated with esophageal squamous cell carcinoma risk Dariush Nasrollahzadeh1,2 , Weimin Ye1,Ramin Shakeri 2, Masoud Sotoudeh2, Shahin Merat2, Farin Kamangar3, Christian C. Abnet 4, Farhad Islami2,5, Paolo Boffetta5, Sanford M. Dawsey4, Paul Brennan6, Reza Malekzadeh*2 1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm
17177, Sweden, 2 Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran,3 Department of Public Health Analysis, School of Community Health and Policy, Morgan State University , Baltimore , Maryland , USA ,4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD
20892-7335, USA,5 Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, NY 10029-6574, USA, 6 International Agency for Research on Cancer, Lyon, France Correspondence to: Professor Reza Malekzadeh, MD. Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, 14117, IRAN,
[email protected] Tel: +982188019008, Fax: +982188012992
Short title: animal contact and esophageal cancer risk
Keywords: Esophageal neoplasm, risk factors, ruminants, animal contact, relative risk
Article category: Epidemiology (short report)
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/ijc.29109
International Journal of Cancer
Page 2 of 19
Novelty and impact: This is the first population-based epidemiologic study conducted in Northern Iran to evaluate the association between prolonged animal contact and risk of esophageal squamous cell carcinoma (ESCC) using validated questionnaire. Contact with ruminants increased ESCC risk 8-fold. Considering the high prevalence of exposure to ruminants in the study area, this association may partially explain the high risk of ESCC in this part of the world.
-
Part of this work has been presented as a poster in UEGW 2012, Amsterdam.
2 John Wiley & Sons, Inc.
Page 3 of 19
International Journal of Cancer
Abstract The etiology of esophageal squamous cell carcinoma (ESCC) in the high risk area of northern Iran is only partially known. We aimed to investigate prolonged animal contact as a risk factor for ESCC in this population. From 2003 to 2007, we administered a validated questionnaire to 300 ESCC cases and 571 randomly selected controls matched for neighborhood of residence, age (± 2 years) and sex. Questions on lifelong exposure to equines, ruminants, canines and poultry, including duration and level of contact, were asked in a face-to-face interviews. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for potential confounders. A total of 94.7% of cases and 68.7% of controls reported lifelong history of contact with ruminants. After controlling for potential confounders, contact with ruminants was associated with an 8-fold increase (95% CI: 3.92 – 14.86) in risk of ESCC, and increments in duration of contact raised the risk estimates in a dose-dependent manner. Contact with equines and poultry did not significantly change associated odds ratio for ESCC risk and contact with ruminants. Odds ratio (95% CI) for contact with canines was 1.99 (1.35-2.93) which after exclusion of contact with ruminants was not significant (OR for contact only with canine: 3.18, 95% CI: 0.73 – 13.17). These results add to the evidence that contact with ruminants may increase the risk of ESCC.
3 John Wiley & Sons, Inc.
International Journal of Cancer
Page 4 of 19
Introduction Esophageal cancer has a very unusual geographical distribution, with the areas of highest incidence occurring across central Asia and from eastern to southern Africa1. At the edge of the so-called Central Asian Esophageal Cancer Belt, the esophageal cancer incidence can vary 10 times over a distance of a few hundred kilometers2. The etiology of ESCC in this endemic area is poorly understood. In contrast to low-risk populations3 , smoking tobacco and heavy alcohol consumption are not dominant risk factors4. In Golestan Province, Iran, at the western end of this endemic area, several environmental risk factors have been identified, including drinking hot tea 5, poor oral health 6, tobacco and opium consumption 7, low socioeconomic status 8 and unexplained high exposure to polycyclic aromatic hydrocarbons9 but it is still unclear whether these risk factors explain the observed high incidence of ESCC in this area. Although studies have shown a significant decline in ESCC incidence in Golestan10, a recent population-based cancer registry has documented that eastern Golestan Province still has age standardized rates (ASRs) of esophageal cancer of 70.7 in men and 42.6 in women11. Contact with animals has been suggested as a potential risk factor for ESCC based on ecologic observations12 , veterinary-based studies and occupational cohort studies. The geographical distribution of the Central Asian Esophageal Cancer Belt is well-matched to a historically nomadic lifestyle which included close contacts with equines, ruminants, canines and poultry. This type of life style is disappearing as socioeconomic status has improved during the last decades. Further suggestive observations are reports of high incidence of esophageal malignancies among animals in endemic areas, including autopsied chickens in Linxian, China 13 and cattle in Kenya 14. Studies of occupational exposure among butchers 15 and workers in poultry 16 or ruminant17 abattoirs or processing plants have shown inconsistent results of 4 John Wiley & Sons, Inc.
Page 5 of 19
International Journal of Cancer
increased risk of mortality due to esophageal cancer, but these studies were often limited by low numbers of cancer cases. Shared environmental resources were suggested as a link between animal and human ESCC in the ecologic observations and exposure to animal viruses were proposed as potential causes for cancer development in the occupational studies. In 2003, we initiated a population-based case-control study to assess the role of previously suggested risk factors and other potential risk factors of ESCC in Golestan Province. In this article we present the results of our evaluation of lifetime contact with domestic and farm animals as a risk factor for ESCC in this region. Material and Methods Details of the study have been reported earlier7. Briefly, case subjects were recruited from December 2003 to June 2007 at the only specialized clinic for esophageal cancer diagnosis and treatment in eastern Golestan. Included cases were histopathologically confirmed ESCC patients who underwent esophagogastroscopy and agreed to participate in the study. The reports of the local cancer registry showed that approximately 70% of all incident cases during the study period were referred to this clinic (unpublished data). Local physicians and health workers in catchment area were asked to refer those who were suspicious for malignancies to this clinic. Additionally controls were matched geographically which would have same referral pattern in case of development of upper gastrointestinal malignancies as recruited cases. Two population-based control subjects, individually matched to the cases by age (± 2 years), sex, and urban neighborhood or village, were selected using the annually-updated family health census. Seventy-seven percent of the enrolled controls were the first selected neighbors, and 11% and 3% were the second and third choices from the lists, respectively. Absence of the eligible
5 John Wiley & Sons, Inc.
International Journal of Cancer
Page 6 of 19
controls at the time of invitation was almost always the reason for not participating in the study. In total, we recruited 300 cases and 571 matched controls. After obtaining written informed consent, a structured questionnaire was administrated face to face by a nurse and a physician. The questionnaire included questions on life-long history of exposure to four groups of animals: equines (horses, mules, donkeys and camels), ruminants (sheep, goats and cattle), dogs and poultry. A detailed history was obtained including the starting and stopping ages and the level of contact with each animal group. Also any changes in types of animals or the levels of contact were recorded. Animal contact was graded into 4 levels. Occasional contact with animals (less than once every two weeks) that were kept within 200 meters of residence or work place was graded as level one. The second level was defined as contact with animals kept in the neighborhood or workplace at least once every two weeks but less than daily. Daily contact with animals (e.g. when animals were kept in the residence or work place) was considered the third level. The fourth level was used for daily close contact with animals, e.g. those who were responsible for jobs such as feeding, cleaning or slaughtering animals on daily basis. Statistical analysis For each animal group (equines, ruminants, dogs, and poultry) total duration was categorized into tertiles based on levels among the exposed controls. Whenever subjects were exposed to more than one animal type, duration of contact with animals was divided by the number of animal types. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Case and control subjects were matched for age, sex and place of residence (urban/rural) by design. Results were further adjusted for potential confounders including education (as a proxy for socioeconomic status),
6 John Wiley & Sons, Inc.
Page 7 of 19
International Journal of Cancer
ethnicity (Turkmen versus non-Turkmen), opium and tobacco use (four categories), fruit and vegetable use, alcohol consumption, source of drinking water (piped-water versus otherwise), use of animal waste as fuel, and family history of cancer. Two-sided P-values ≤ 0.05 were considered as statistically significant. All statistical analyses were performed using STATA, version 12.0 (StataCorp, College Station, TX). The study was approved by the ethical committee of the Digestive Disease Research Institute of Tehran University of Medical Sciences, Iran; the Institutional Review Board of the National Cancer Institute, USA; the Institutional Review Board of the International Agency for Research on Cancer, France; and the Stockholm Regional Ethics Vetting Board, Sweden. Results The study included 300 incident case patients and 571 matched control subjects, from whom animal contact history was available for 287 (96%) cases and 542 (95%) controls. Of the 42 subjects (13 cases, 29 controls) with a missing history of animal contact, 18 case-control pairs were missing, due to lack of information on cases in 13 pairs and lack of exposure data on controls in 5 pairs. For the rest of the subjects with missing data, at least one control for each matched-pair existed. A total of 19 subjects (8 cases and 11 controls) reported having contact with more than one animal type without further specification; there was no association with risk of ESCC among this group (OR: 1.87, 95% CI: 0.62-5.69) and they were excluded when association with a particular type of animal was investigated. Table 1 summarizes the demographic characteristics of participants and the distribution of potential confounders. Among demographic variables and potential confounders ESCC subjects in study area were less educated , consumed more tobacco/opium , had less access to piped water, more likely to have a
7 John Wiley & Sons, Inc.
International Journal of Cancer
Page 8 of 19
relative with history of cancer and consuming hot tea (Table 1). No substantial difference was observed in these variables between subjects with available and missing history of exposure to animals. Table 2 shows the association of exposure to the four groups of animals in ESCC cases and matched controls and the corresponding crude and adjusted ORs (95% CI). An equal proportion of cases and controls resided in rural areas (73%, 74%), and proportions of exposure to equines and poultry were essentially identical among cases and controls. However exposure to the ruminants and canines was significantly greater among ESCC cases than among controls: 94.7% of cases and only 68.7% of controls were exposed to ruminants, and 70.8% of cases and 52.7% of controls were exposed to canines (both P-values 70 years old, showed that higher proportions of these subgroups were exposed to all animal types except poultry as the age increased. For example, the proportions of controls who were exposed to ruminants in these four age groups were 51.1%, 68.5%, 65.5% and 75.5%, respectively. Exposure to different animal types overlapped among participants. To investigate whether exposure to a greater number of different types of animals could change the risk, we compared exposure to 2, 3 and 4 different types of animals with exposure to only one type as the reference group. The odds ratios (95%CI) for two animal types was 3.04 (1.54-6.0), for three animal types was 3.85 (1.96 -7.58) and for four animal types was 3.31 (1.86 -5.91). The observed risk was constant, without any trend. After exclusion of those who had contact with ruminants, the risk of ESCC for exposure to other type of animals disappeared from all strata, and the ORs (95% CIs) for contact with 2 and 3 types of animals were 0.46 (0.14 – 1.49) and 0.29 (0.04 – 1.78), respectively, based on limited numbers of observations. Discussion We found more than an 8-fold increased risk of ESCC among those who were in contact with domesticated ruminants, and increments in duration of contact raised the risk estimates in a dosedependent manner.
9 John Wiley & Sons, Inc.
International Journal of Cancer
Page 10 of 19
Most domestic animals in Golestan were kept at rural houses, so a neighborhood/village-matched design was appropriate for this study. Selection of controls from the same residential village as the cases made it less important for us to collect information about soil, source of pasture for grazing, plant coverage or use of pesticides or herbicides, as these variables were likely to be homogenous in these restricted geographical areas. Evaluated separately, contact with canines also increased the risk of ESCC, by approximately 2fold. This exposure variable included contact with both domestic and stray wild dogs. Wild dogs are distributed throughout the study area, while domestic dogs are mainly used by villagers to guard ruminants, which may help explain the observed association of overall canine contact and ESCC risk. After evaluating the exposure of ruminants and dogs together, the risk due only to canines no longer persisted and no excess risk was attributable to the contact with both animals compared to ruminants alone. A previous study of a cohort of workers in ruminant slaughter plants reported a significantly higher standardized mortality ratio) for esophageal cancer 17. The same group also reported an excess risk of esophageal cancer among poultry workers 16. One explanation for our ruminant findings could be exposure to ruminants’ waste products, since industrial standards of animal waste disposal are not common among villagers who keep animals within their households. Another factor could be exposure to ruminants’ milk. An early nutritional study showed higher consumption of sheep’s and goat’s milk in northern Iran than in lower risk areas 18. Another study showed that small ruminants fed by a family of Euphorbiaceae flower plants extract contained diterpene esters, a group of compounds which showed promoting activity in experimental systems, from their milk 19. This genus is one of the most species-rich
10 John Wiley & Sons, Inc.
Page 11 of 19
International Journal of Cancer
flowering plants, and several of its species occur in the study area 20. Another possible explanation for our findings is exposure to animal zoonoses, e.g. viruses that can cause cancer in ruminants. Ruminant viruses have already been shown or suspected to cause tumors of the alimentary tract (bovine papillomas) 21 and upper aerodigestive tract (ovine nasal adenocarcinoma) 22 or colorectal cancer 23. Although 58% of human pathogens are zoonotic 24, it is not clear whether ruminant viruses are transmissible to humans or within human populations, or whether they can cause cancer in humans. In addition to the multi-host nature of some zoonoses, the transmission pattern can be complex, e.g. having rodents as carriers or wild animals as sources. Alternatively, contact with ruminants can be a marker of other, still undetermined risk factors related to traditional lifestyle and low socioeconomic status. Other observations support our finding of high levels of contact between humans and animals in study area. Golestan province has the highest incidence of animal bite, animal rabies and hydatidosis among the Iranian provinces bordering the Caspian Sea 25. The population of domesticated ruminants in the catchment area during the study period was 1,733,000 with 83% small ruminants (74% sheep and 9% goat) and 17% cattle. We did not collect information on contact with individual types of ruminants, so we are not able to determine the individual ruminant contributions to the observed group association. Most of our subjects were exposed to ruminants from birth. Additionally, based on the observed common lifestyle of these people, we can speculate that subjects may also have been exposed to ruminants’ materials prenatally. The median duration of contact with ruminants was 54 years.
11 John Wiley & Sons, Inc.
International Journal of Cancer
Page 12 of 19
Our study included a well-defined population, with 70% of the incident ESCC cases in the catchment area.Another study from Cancer Institute of Iran26 showed very similar characteristics to the recruited patients27;i.e. similar stage (10% in early stage), gender proportion (45-50% Female) and age. Although there is no direct data available to compare recruited subjects to those who did not visit clinic, due to homogenous population and similar socioeconomic conditions, in addition to indirect evidences from cancer registry-based study26, it is improbable that nonrecruited cases would dramatically different form recruited subjects. Additionally, as controls were matched geographically, they would follow same referral pattern in case of developing symptoms . There was an 88% response rate among first and second randomly selected neighborhood controls. Detailed information on known confounders was collected through validated questionnaires. Neither interviewees nor interviewers were aware of a hypothesis linking exposure to animals and ESCC risk. One of the limitations of the study was the modest number of individuals in some of the reference groups, due to the homogenous exposure pattern among many study subjects, which could lead to less precision of our estimates i.e. due to small number of ESCC cases in the category of no contact with ruminants, our point estimates of the risk associated with higher level or longer period of contact with ruminants might not be precise. Because of the same limitation, our estimate of dose-response association with level of contact might not be as precise as duration. Another potential limitation was co-exposure to other animals when studying ruminants, due to the high prevalence of exposure to this group of animals in the study area. Our findings suggest that long-term contact with ruminants is associated with an increased risk of ESCC among our study population. Additional studies of this association in other populations
12 John Wiley & Sons, Inc.
Page 13 of 19
International Journal of Cancer
and further investigation of possible zoonotic sources of ESCC risk in our high risk area are warranted. Funding This work was supported by the Digestive Disease Research Center of Tehran University of Medical Sciences (grant 82-603) and by intramural funds from the National Cancer Institute at the National Institutes of Health. D.N. was supported by a KID scholarship from Karolinska Institute. Acknowledgement We thank our colleagues at Atrak Clinic and the local health networks and health workers (Behvarz) in the study area for their contribution to this study.
13 John Wiley & Sons, Inc.
International Journal of Cancer
Page 14 of 19
References
1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61: 69-90. 2. Kmet J, Mahboubi E. Esophageal cancer in the Caspian littoral of Iran: initial studies. Science 1972;175: 846-53. 3. Freedman ND, Abnet CC, Leitzmann MF, Mouw T, Subar AF, Hollenbeck AR, Schatzkin A. A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol 2007;165: 1424-33. 4. Tran GD, Sun XD, Abnet CC, Fan JH, Dawsey SM, Dong ZW, Mark SD, Qiao YL, Taylor PR. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer 2005;113: 456-63. 5. Islami F, Pourshams A, Nasrollahzadeh D, Kamangar F, Fahimi S, Shakeri R, Abedi-Ardekani B, Merat S, Vahedi H, Semnani S, Abnet CC, Brennan P, et al. Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study. Bmj 2009;338: b929. 6. Abnet CC, Kamangar F, Islami F, Nasrollahzadeh D, Brennan P, Aghcheli K, Merat S, Pourshams A, Marjani HA, Ebadati A, Sotoudeh M, Boffetta P, et al. Tooth loss and lack of regular oral hygiene are associated with higher risk of esophageal squamous cell carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2008;17: 3062-8. 7. Nasrollahzadeh D, Kamangar F, Aghcheli K, Sotoudeh M, Islami F, Abnet CC, Shakeri R, Pourshams A, Marjani HA, Nouraie M, Khatibian M, Semnani S, et al. Opium, tobacco, and alcohol use in relation to oesophageal squamous cell carcinoma in a high-risk area of Iran. British journal of cancer 2008;98: 1857-63. 8. Islami F, Kamangar F, Nasrollahzadeh D, Aghcheli K, Sotoudeh M, Abedi-Ardekani B, Merat S, Nasseri-Moghaddam S, Semnani S, Sepehr A, Wakefield J, Moller H, et al. Socio-economic status and oesophageal cancer: results from a population-based case-control study in a high-risk area. Int J Epidemiol 2009;38: 978-88. 9. Abedi-Ardekani B, Kamangar F, Hewitt SM, Hainaut P, Sotoudeh M, Abnet CC, Taylor PR, Boffetta P, Malekzadeh R, Dawsey SM. Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran. Gut 2010;59: 1178-83. 10. Semnani S, Sadjadi A, Fahimi S, Nouraie M, Naeimi M, Kabir J, Fakheri H, Saadatnia H, Ghavamnasiri MR, Malekzadeh R. Declining incidence of esophageal cancer in the Turkmen Plain, eastern part of the Caspian Littoral of Iran: a retrospective cancer surveillance. Cancer detection and prevention 2006;30: 14-9. 11. Roshandel G, Sadjadi A, Aarabi M, Keshtkar A, Sedaghat SM, Nouraie SM, Semnani S, Malekzadeh R. Cancer incidence in Golestan Province: report of an ongoing population-based cancer registry in Iran between 2004 and 2008. Archives of Iranian medicine 2012;15: 196-200. 12. Sagar PM. Aetiology of cancer of the oesophagus: geographical studies in the footsteps of Marco Polo and beyond. Gut 1989;30: 561-4. 13. Rubio CA, Liu FS. Spontaneous squamous carcinoma of the esophagus in chickens. Cancer 1989;64: 2511-4. 14. Plowright W. Malignant neoplasia of the oesophagus and rumen of cattle in Kenya. Journal of comparative pathology 1955;65: 108-14.
14 John Wiley & Sons, Inc.
Page 15 of 19
International Journal of Cancer
15. Boffetta P, Gridley G, Gustavsson P, Brennan P, Blair A, Ekstrom AM, Fraumeni JF, Jr. Employment as butcher and cancer risk in a record-linkage study from Sweden. Cancer causes & control : CCC 2000;11: 627-33. 16. Johnson ES, Shorter C, Rider B, Jiles R. Mortality from cancer and other diseases in poultry slaughtering/processing plants. International journal of epidemiology 1997;26: 1142-50. 17. Johnson ES. Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants. Environment international 2011;37: 950-9. 18. Hormozdiari H, Day NE, Aramesh B, Mahboubi E. Dietary factors and esophageal cancer in the Caspian Littoral of Iran. Cancer research 1975;35: 3493-8. 19. Zayed SM, Farghaly M, Taha H, Gminski R, Hecker E. Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). III. Milk of lactating goats fed on the skin irritant herb Euphorbia peplus is polluted by tumor promoters of the ingenane diterpene ester type. Journal of cancer research and clinical oncology 1998;124: 301-6. 20. Pahlevani AH, Riina R. A synopsis of Euphorbia subgen. Chamaesyce (Euphorbiaceae) in Iran. Ann Bot Fenn 2011;48: 304-16. 21. Campo MS. Papillomas and Cancer in Cattle. Cancer Surv 1987;6: 39-54. 22. Cousens C, Thonur L, Imlach S, Crawford J, Sales J, Griffiths DJ. Jaagsiekte sheep retrovirus is present at high concentration in lung fluid produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for several weeks at ambient temperatures. Res Vet Sci 2009;87: 154-6. 23. zur Hausen H. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. Int J Cancer 2012;130: 2475-83. 24. Woolhouse MEJ, Gowtage-Sequeria S. Host range and emerging and reemerging pathogens. Emerging infectious diseases 2005;11: 1842-7. 25. Mazaheri V HNK, Simani S, Yunesian M, Fayaz A, Biglari P, Mostafavi E. Geographical distribution of animal bite and rabies in the Caspian Sea littoral provinces during 2002-2007. Journal of School of Public Health and Institute of Public Health Research 2010;8: 37-46. 26. Mir MR, Rajabpour MV, Delarestaghi MM, Hadji M, Harirchi I, Mir P, Mir A, Lashkari M, Zendehdel K. Short- and long-term survival of esophageal cancer patients treated at the Cancer Institute of Iran. Dig Surg 2013;30: 331-6. 27. Aghcheli K, Marjani HA, Nasrollahzadeh D, Islami F, Shakeri R, Sotoudeh M, Abedi-Ardekani B, Ghavamnasiri MR, Razaei E, Khalilipour E, Mohtashami S, Makhdoomi Y, et al. Prognostic factors for esophageal squamous cell carcinoma--a population-based study in Golestan Province, Iran, a high incidence area. PLoS One 2011;6: e22152.
15 John Wiley & Sons, Inc.
International Journal of Cancer
Page 16 of 19
Table 1. Characteristics of esophageal squamous cell carcinoma cases and matched controls Characteristic Age years; mean (SD) Sex (%) Males Females Residence area (%) Urban Rural Ethnicity (%) Turkmen Non-Turkmen Education (%) Illiterate Primary school/higher Alcohol ever use (%) No Yes Tobacco and opium, ever use (%)1 Neither Tobacco only Opium only Tobacco and opium Fruit and vegetable consumption (%) ≤ median > median Use of animal waste fuel life time1 No Yes Access to piped water source Yes No Family history of cancer No Yes Tea drinking habit Cool Warm Hot missing
Controls (n=531) 64.4 (10.4)
Cases (n=281) 64.5 (11.1)
P value
257 (48.4) 274 (51.6)
139 (49.5) 142 (50.5)
141 (26.5) 390 (73.4)
72 (25.6) 209 (74.4)
0.77
288 (54.2) 243 (45.8)
164 (58.4) 117 (41.6)
0.26
438 (82.5) 93 (17.5)
257 (91.5) 24 (8.5)
0.001
518 (97.6) 13 (2.4)
275 (97.9) 6 (2.1)
0.78
369 (69.5) 62 (11.7) 34 (6.4) 66 (12.4)
157 (56.1) 39 (13.9) 28 (10.0) 56 (20.0)
0.001
238 (44.8) 293 (55.2)
133 (47.3) 148 (52.7)
0.49
494 (93.2) 36 (6.8)
265 (94.6) 15 (54)
0.42
481 (90.6) 50 (9.4)
206 (73.3) 75 (26.7)
0.0001
439 (82.7) 92 (17.3)
193 (68.7) 88 (31.3)
< 0.0001
362 (68.2) 149 (28.0) 18 (3.4) 2 (0.4)
117 (41.7) 103 (36.6) 61 (21.7) 0
< 0.0001
John Wiley & Sons, Inc.
Page 17 of 19
International Journal of Cancer
Table 2. Animal contact among esophageal squamous cell carcinoma cases and matched controls
Equines Never Ever Duration No contact 1st tertile 2nd tertile 3rd tertile Level of contact Never or limited level 2 level 3 level 4 missing Ruminants Never Ever Duration2 No contact 1st tertile 2nd tertile 3rd tertile Level of contact3 Never or limited level 2 level 3 level 4 missing Canines Never Ever Duration No contact 1st tertile 2nd tertile 3rd tertile Level of contact Never or limited level 2 level 3 level 4 missing Poultry
Controls (%)
Cases (%)
Crude OR (95%CI)
Adjusted1 OR (95%CI)
234 (44.1) 297 (55.9)
121 (43.1) 160 (56.9)
Referent 1.04 (0.77-1.41)
Referent 0.96 (0.67-1.38)
234 (44.1) 112 (21.1) 92 (17.3) 93 (17.5)
121 (43.1) 59 (21.0) 59 (21.0) 42 (14.9)
Referent 1.07 (0.73-1.59) 1.22 (0.81-1.83) 0.81 (0.50-1.31)
Referent 1.08 (0.67-1.71) 0.97 (0.59-1.60) 0.77 (0.43-1.39)
235 (44.3) 17 (3.2) 142 (26.7) 123 (23.2) 14 (2.6)
124 (44.1) 5 (1.8) 63 (22.4) 89 (31.7) 0
Referent 0.61 (0.20-1.90) 0.85 (0.58-1.24) 1.57 (1.05-2.36)
Referent 0.42 (0.11-1.66) 0.80 (0.51-1.26) 1.44 (0.87-2.40)
166 (31.3) 365 (68.7)
15 (5.3) 266 (94.7)
Referent 9.06 (4.94-16.61)
Referent 7.63 (3.92-14.86)
166 (31.3) 124 (23.3) 122 (23.0) 119 (22.4)
15 (5.3) 87 (31.0) 83 (29.5) 96 (34.2)
Referent 8.13 (4.23-15.62) 8.71 (4.48-16.93) 11.70 (5.91-23.11)
Referent 5.74 (2.76-11.91) 7.87 (3.70-16.75) 12.02 (5.54-26.10)
167 (31.5) 10 (1.9) 85 (16.0) 262 (49.3) 7 (1.3)
16 (5.7) 5 (1.8) 81 (28.8) 179 (63.7) 0
Referent 4.95 (1.33-18.51) 9.92 (5.15-19.10) 8.11 (4.42-14.89)
Referent 1.97 (0.35-10.98) 8.10 (3.86-16.93) 6.84 (3.42-13.68)
251 (47.3) 280 (52.7)
82 (29.2) 199 (70.8)
Referent 2.06 (1.50-2.84)
Referent 1.99 (1.35-2.93)
251 (47.3) 99 (18.6) 88 (16.6) 93 (17.5)
82 (29.2) 64 (22.8) 48 (17.0) 87 (31.0)
Referent 1.85 (1.20-2.85) 1.49 (0.95-2.34) 3.14 (2.03-4.86)
Referent 2.00 (1.19-3.37) 1.29 (0.75-2.24) 3.16 (1.84-5.44)
253 (47.6) 61 (11.5) 200 (37.7) 12 (2.3) 5 (0.9)
84 (29.9) 9 (3.2) 176 (62.6) 67 (22.3) 0
Referent 0.46 (0.21-0.99) 2.50 (1.79-3.50) 2.66 (1.10-6.41)
Referent 0.33 (0.12-0.914) 2.43 (1.60-3.70) 2.90 (1.02-8.20)
John Wiley & Sons, Inc.
International Journal of Cancer
Page 18 of 19
Never 69 (13.0) 35 (12.5) Referent Referent Ever 462 (87.0) 246 (87.5) 1.00 (0.62-1.59) 0.96 (0.53-1.77) Duration No contact 69 (13.0) 35 (12.5) Referent Referent st 1 tertile 155 (29.2) 101 (35.9) 1.12 (0.67-1.87) 0.98 (0.50-1.92) 2nd tertile 150 (28.2) 107 (38.1) 1.28 (0.76-2.16) 1.32 (0.68-2.56) 3rd tertile 152 (28.6) 38 (13.5) 0.46 (0.25-0.83) 0.43 (0.20-1.00) missing 5 (1.0) 0 Level of contact Never or limited 75 (14.1) 36 (12.8) Referent Referent level 2 19 (3.6) 3 (1.1) 0.30 (0.1-1.11) 0.22 (0.04-1.14 ) level 3 297 (55.9) 152 (54.1) 0.97 (0.59-1.58) 0.98 (0.52-1.85) level 4 131 (24.7) 89 (31.7) 1.59 (0.93-2.73) 1.46 (0.72-2.95) missing 9 (1.7) 1 (0.3) OR: odds ratio; 95% CI: 95% confidence interval. Odds ratios were obtained from conditional logistic regression models. 1 Adjusted for potential confounders including education (as a proxy for socioeconomic status), ethnicity (Turkmen versus non-Turkmen), opium and tobacco use (four categories), alcohol consumption, source of drinking water (piped water versus otherwise) , use of animal waste as fuel, family history of cancer, and tea drinking habit (cool, warm, hot). 23 , P for trend for contact duration = 0.017 , P for trends was calculated using conditional
logistic regression model after removing no-contact group from model. P for trend for level of contact with ruminants after removal of no-contact group was not significant (p=0.93)”.
John Wiley & Sons, Inc.
Page 19 of 19
International Journal of Cancer
Table 3. The association between contact with ruminants and domestic canine, alone or in combination, and esophageal squamous cell carcinoma Canines and ruminants Canine- RuminantCanine+ RuminantCanine- Ruminant+ Canine+ Ruminant+
Controls (%) 140 (26.4) 26 (4.9) 111 (20.9) 254 (47.8)
Cases (%) 10 (3.6) 5 (1.8) 72 (25.6) 194 (69.0)
Crude OR (95%CI) Referent 3.31 (0.91-12.02) 12.70 (5.66-28.46) 11.76 (5.65-24.49)
1
Adjusted1 OR (95%CI) Referent 3.18 (0.73-13.17) 10.62 (4.32-26.13) 9.81 (4.41-21.78)
Adjusted for potential confounders including education (as a proxy for socioeconomic status), ethnicity (Turkmen versus non-Turkmen), opium and tobacco use (four categories), alcohol consumption, source of drinking water (piped water versus otherwise), use of animal waste as fuel, family history of cancer, and tea drinking habit (cool, warm and hot)
John Wiley & Sons, Inc. View publication stats
